Process for producing optically active compound

ABSTRACT

A process for producing an optically active compound based on the hydrolysis of an alkenyl ester compound or the cleavage of an alkenyl ether compound. The process uses neither an acidic compound nor a basic compound, and rectants can be reacted in a high concentration. It does not necessitate a buffer, nutrient, etc. unlike enzymatic reactions or reactions using a microorganism. It is a simple process which attains a satisfactory production efficiency. The process, which is for producing an optically active carboxylic acid or optically active alcohol represented by the general formula (VI): (wherein R 1 , R 2 , and R 3  are different groups; and A represents methylene, carbonyl, or a single bound), is characterized by causing water to act on an alkenyl ester or alkenyl ether represented by the general formula (I): (wherein R 4 , R 5 , and R 6  each represents hydrogen, alkyl, etc.) in the presence of a specific transition metal complex having an optically active ligand.

TECHNICAL FIELD

The present invention relates to a novel process for producing anoptically active compound, and particularly to a process for producingan optically active compound by cleaving a carbon-oxygen bond of alkenylesters or alkenyl ethers by using a metal complex having an opticallyactive ligand as a catalyst.

BACKGROUND ART

Generally, a hydrolysis of vinyl esters and a cleavage of vinyl ethersare conducted in the presence of an acid or basic catalyst. However,this method cannot be used when a functional group or a protective groupwhich is sensitive to an acid or a base is present.

Thus, methods using enzymes or microorganisms other than chemicalmeasures are known as mild methods (see, for example, Prior ArtReference 1).

There are also studies of artificial enzymes to reproduce enzymaticfunctions by an artificially synthesized molecule though these enzymesare still impractical to use (see, for example, Prior Art Reference 2).

However, in the methods using an enzyme reaction or a reaction usingartificial enzyme, substrate concentration is usually about 0.1% toseveral % by weight. The reaction is therefore conducted in aconsiderably diluted solution, resulting in low reaction efficiency.

Moreover, in enzyme reactions or reactions using microorganisms, it isnecessary for the pH of the solution to be adjusted by using aconsiderable amount of a buffer solution, and in many reactions,nutrient source is also required.

Examples using metal compounds are also known, i.e., a method in whichpropenyl ether is cleft in a mild condition by using a palladiumcompound and a copper compound to obtain alcohols. However, only aracemate can be obtained in this method (see, for example, Prior ArtReference 3).

The prior arts relating to the present invention are as follows, and thefollowing documents are incorporated as reference in this specification.

1. Luzzio. F. A etc., Tetrahedron: Asymmetry, 2002, 1173-1180

2. Zhang. B.; J. Am. Chem. Soc., 1997, 119, 1676-1681

3. Mareyala, H. B. stc., Tetrahedron, Vol. 53, 17501-17512, 1997

DISCLOSURE OF THE INVENTION

An object of the present invention is to provide a process for producingan optical active compound by using a hydrolysis of alkenyl esters and acleavage of alkenyl ethers, and the process which is simple and has highproduction efficiency, reacting at high concentrations and necessitatingneither a buffer solution nor a nutrient source unlike an enzymereaction and a reaction using microorganisms

BEST MODE FOR CARRYING OUT THE INVENTION

After intensive studies to solve the problems above, the inventors havefound that various metal complexes having an optically active ligandcleave a carbon-oxygen bond in alkenyl esters and alkenyl ethers toobtain an optically active carboxylic acid or alcohol from a racemic rawmaterial, and completed the present invention.

Accordingly, the present invention relates to a process for producing anoptically active compound represented by the following formula (VI), theprocess comprising reacting water with a compound represented by thefollowing formula (I) in the presence of one or more transition metalcomplexes having, as a ligand, an optically active compound representedby the following formula (II), (III), (IV) or (V):

(wherein R¹, R² and R³, which are different from each other, represent ahydrogen atom, a straight-chain, branched-chain or cyclic alkyl groupwhich may be substituted, a straight-chain, branched-chain or cyclicalkenyl group which may be substituted, a straight-chain orbranched-chain alkoxy group which may be substituted, an aralkyl groupwhich may be substituted, an aryl group which may be substituted, aheterocyclic group which may be substituted, a straight-chain orbranched-chain alkoxycarbonyl group which may be substituted, anaralkyloxy group which may be substituted, an alkanoyloxy group whichmay be substituted, an alkylthio group which may be substituted, anaralkylthio group which may be substituted, a benzoyloxy group which maybe substituted, a tri-substituted silyloxy group, an amino group whichmay be substituted, a hydroxyl group, a tetrahydropyran-2-yloxy group ora mercapto group: any two of R¹, R² and R³ may form a ring which maycontain a heteroatom therein; and R⁴, R⁵ and R⁶ each independentlyrepresent a hydrogen atom, a straight-chain, branched-chain or cyclicalkyl group which may be substituted, a straight-chain, branched-chainor cyclic alkenyl group which may be substituted, an aralkyl group whichmay be substituted, an aryl group which may be substituted, aheterocyclic group which may be substituted, a straight-chain orbranched-chain alkoxycarbonyl group which may be substituted, anaryloxycarbonyl group which may be substituted or an aralkyloxycarbonylgroup which may be substituted; R⁴ and R⁵ or R⁵ and R⁶ may be combinedwith each other together with an adjacent carbon atom having a doublebond to form a ring; and A represents a methylene group, a carbonylgroup or a single bond);

(wherein Ar¹ and Ar² each independently represent a phenyl group whichmay be substituted, R⁸ and R⁹ each independently represent a methylgroup or a methoxy group, and R⁷ and R¹⁰ represent a hydrogen atom; R⁷and R⁸ and/or R⁹ and R¹⁰ may be combined with each other to form a ringwhich may contain a heteroatom therein);

(wherein R¹¹ and R¹² each independently represent a hydrogen atom or amethyl group, R¹³, R¹⁴, R¹⁵ and R¹⁶ each independently represent ahydrogen atom or an alkyl group and, * represents an asymmetric carbonatom);

(wherein R¹⁷ and R¹⁸ each independently represent an alkyl group or aphenyl group and,* represents an asymmetric carbon atom);

(wherein R¹⁹ represents an alkyl group or a phenyl group, Ar³ representsa phenyl group which may be substituted, and * represents an asymmetriccarbon atom), and

(wherein R¹, R² and A have the same meanings as above, and * representsan asymmetric carbon atom.)

The present invention is hereinafter explained in detail.

The production process according to the present invention is a processof producing an optically active carboxylic acid or an optically activealcohol represented by the formula (VI) by reacting water with analkenyl ester or an alkenyl ether represented by the formula (I) in thepresence of a transition metal complex having an optically activeligand.

In the formula (I), when A is a carbonyl group, the above process iscarried out by the hydrolysis of alkenyl esters to produce an opticallyactive carboxylic acid and when A is a methylene group or a single bond,the process is by the cleavage of alkenyl ethers to produce an opticallyactive alcohol.

In the above formulae (I) and (VI), examples of the alkyl group of thestraight-chain, branched-chain or cyclic alkyl group which may besubstituted, which is represented by R¹, R² and R³, includestraight-chain, branched-chain or cyclic alkyl groups having 1 to 10carbon atoms, preferably 1 to 6 carbon atoms. Specific examples of thesealkyl groups include a methyl group, ethyl group, n-propyl group,isopropyl group, n-butyl group, isobutyl group, sec-butyl group,tert-butyl group, 3,3-dimethyl-2-butyl group, pentyl group, hexyl group,octyl group, decyl group, cyclopropyl group, cyclopentyl group,cyclohexyl group, cyclooctyl group and 2-bornyl group.

Examples of the alkenyl group of the straight-chain, branched-chain orcyclic alkenyl group which may be substituted include straight-chain,branched-chain or cyclic alkenyl groups having 3 to 10 carbon atoms,preferably 3 to 6 carbon atoms. Specific examples of these alkenylgroups include a 2-propenyl group, 2-butenyl group, 1-methyl-3-butenylgroup, 5-hexenyl group, 3- or 4-cyclopentenyl group and 3- or4-cyclohexenyl group.

Examples of the alkoxy group of the straight-chain or branched-chainalkoxy group which may be substituted include straight- orbranched-chain alkoxy groups having 1 to 10 carbon atoms,preferably 1 to6 carbon atoms. Specific examples of these alkoxy groups include amethoxy group, ethoxy group, isopropoxy group, tert-butoxy group,2,2-dimethylpropoxy group and hexyloxy group.

Examples of the aralkyl group of the aralkyl group which maybesubstituted include aralkyl groups having 7 to 20 carbon atoms,preferably 7 to 15 carbon atoms. Specific examples of these aralkylgroups include a benzyl group, α-methylbenzyl group, phenethyl group,4-methylbenzyl group, naphthylmethyl group and naphthylethyl group.

Examples of the aryl group of the aryl group which may be substitutedinclude aryl groups having 6 to 20 carbon atoms, preferably 6 to 14carbon atoms. Specific examples of the these aryl groups include aphenyl group, tolyl group, xylyl group, naphthyl group, methylnaphthylgroup, anthryl group, phenanthryl group and biphenyl group.

Examples of the heterocyclic group of the heterocyclic group which maybe substituted include saturated or unsaturated monocyclic, polycyclicor fused heterocyclic groups which have one or more nitrogen atoms,oxygen atoms and/or sulfur atoms in a ring wherein the number of ringmembers is 5 to 20, preferably 5 to 10 and may be condensed with acarbon cyclic group such as a cycloalkyl group, cycloalkenyl group oraryl group. Specific examples of these heterocyclic groups include a1,3-dioxolan-4-yl group, 2,2-dimethyl-1,3-dioxolan-4-yl group,2-oxo-1,3-dioxolan-4-yl group, pyrrolidyl group, piperidyl group,piperidino group, piperazil group, morpholino group, morpholinyl group,pyridyl group, thienyl group, phenylthienyl group, thiazolyl group,oxazolidyl group, furyl group, pyrrolyl group, imidazolyl group, indolylgroup, quinolyl group and pyrimidyl group.

Examples of the alkoxycarbonyl group of the alkoxycarbonyl group whichmay be substituted include straight-chain or branched-chainalkoxycarbonyl groups having 2 to 7 carbon atoms. Specific examples ofthese alkoxycarbonyl groups include a methoxycarbonyl group,ethoxycarbonyl group, n-propoxycarbonyl group, isopropoxycarbonyl group,n-butyloxycarbonyl group, tert-butyloxycarbonyl group andn-hexyloxycarbonyl group.

Examples of the aralkyloxy group of the aralkyloxy group which may besubstituted include aralkyloxy groups having 7 to 20 carbon atoms,preferably 7 to 15 carbon atoms. Specific examples of these aralkyloxygroups include a benzyloxy group, 1-phenetyloxy group andnaphthylmethyloxy group.

Examples of the alkanoyloxy group of the alkanoyloxy group which may besubstituted include alkanoyloxy groups having 1 to 6 carbon atoms.Specific examples of these alkanoyloxy groups include an acetoxy group,propionyloxy group, pivaloyloxy group and hexanoyloxy group.

Examples of the alkylthio group of the alkylthio group which may besubstituted include alkylthio groups having 1 to 4 carbon atoms.Specific examples of these alkylthio groups include a methylthio group,ethylthio group, isopropylthio group and tert-butylthio group.

Examples of the aralkylthio group of the aralkylthio group which may besubstituted include aralkylthio groups having 7 to 20 carbon atoms,preferably 7 to 15 carbon atoms. Specific examples of these aralkylthiogroups include a benzylthio group, 1-phenetylthio group andnaphthylmethylthio group.

The substituents of these alkyl group, alkenyl group, alkoxy group,aralkyl group, aryl group, heterocyclic group and the like,alkoxycarbonyl group, aralkyloxy group, alkanoyloxy group, alkylthiogroup or aralkylthio group may be any substituent as far as it is nodisadvantageous to the reaction according to the present invention.Examples of the substituent include an alkyl group having 1 to 4 carbonatoms, alkoxy group having 1 to 4 carbon atoms, halogen atom,trifluoromethyl group, phenyl group, benzyl group, hydroxyl group,alkoxycarbonyloxy group having 1 to 4 carbon atoms, benzoyl group,benzyloxy group, methoxymethyl group, 2H-tetrahydropyran-2-yloxy group,trimethylsilyloxy group, tert-butyldimethylsilyloxy group,benzyloxycarbonyloxy group, oxirane-2-yl group, 1,3-dioxolan-4-yl group,2-oxo-1,3-dioxolan-yl group, amino group, dimethylamino group,diethylamino group, acetoxyamino group, benzyloxycarbonylamino group,anilino group and benzylamino group.

Specific examples of the benzoyloxy group which may be substituted,which is represented by R¹, R² and R³ in the above formulae (I) and(VI), include a benzoyloxy group, 4-toluoyloxy group, 4-anisoyloxygroup, 4-nitrobenzoyloxy group, 4-chlorobenzoyloxy group and2,4,6-trichlorobenzoyloxy group.

Specific examples of the tri-substituted silyloxy group include atrimethylsilyloxy group, triethylsilyloxy group, triisopropylsilyloxygroup, tert-butyldimethylsilyloxy group and triphenylsilyloxy group.

Specific examples of the amino group which may be substituted include anamino group and mono-substituted amino groups such as a methylaminogroup, ethylamino group and benzylamino group, di-substituted aminogroup such as a dimethylamino group, diethylamino group anddibenzylamino group, amide groups such as an acetylamino group orbenzoylamino group and urethane groups such as a benzyloxycarbonylaminogroup.

Examples of the ring formed of any two of R¹, R² and R³ include five- orsix-membered cycloalkanes having a substituent, C₇-C₁₂ bicycloalkaneshaving a substituent, three- to six-membered hetero rings and indanerings.

Examples of five- or six-membered cycloalkanes having a substituentinclude 2-methylcyclopentane, 2,2-dimethylcyclopentane,2-tert-butylcyclohexane, 4-tert-butylcyclohexane, 2-phenylcyclohexane,2-aminocyclopentane, 2-acetylaminocyclohexane,2-methylaminocyclopentane, 2-hydroxycyclohexane and2-acetoxycyclohexane. Examples of C₇-C₁₂ bicycloalkanes having asubstituent include 2-norbornane and bornane and examples of the three-to six-membered hetero ring include oxirane, 1,3-dioxolane,2,2-dimethyl-1,3-dioxolane, 2-oxo-1,3-dioxolane, pyrrolidine ring andpiperidine ring. Examples of the indane ring include indane,1-aminoindane and 1-acetylaminoindane.

In the above formula (I), the definitions and specific examples of thestraight-chain, branched-chain or cyclic alkyl group which may besubstituted, straight-chain, branched-chain or cyclic alkenyl groupwhich may be substituted, aralkyl group which may be substituted, arylgroup which may be substituted, heterocyclic group which may besubstituted and alkoxycarbonyl group which may be substitutedrepresented by R⁴, R⁵ and R⁶ are the same as those of the above R¹, R²or R³. Further, the substituents of these alkyl group, alkenyl group,aralkyl group, aryl group, heterocyclic group and alkoxycarbonyl groupmay be any substituent as far as it is no disadvantageous to thereaction according to the present invention, as well as in R¹, R² andR³. Specific examples of the substituent of these groups are the same asthose of the substituent of R¹, R² or R³.

In the above formula (I), examples of the aryloxycarbonyl group of thearyloxycarbonyl group which may be substituted, which is represented byR⁴, R⁵ or R⁶, include aryloxycarbonyl groups having 7 to 15 carbonatoms. Specific examples of the aryloxycarbonyl group which may besubstituted include a phenoxycarbonyl group, tolyloxycarbonyl group,xylyloxycarbonyl group, naphthyloxycarbonyl group,methoxyphenyloxycarbonyl group, fluorophenyloxycarbonyl group,trifluoromethylphenyloxycarbonyl group, dimethylaminophenyloxycarbonylgroup, acetylaminophenyloxycarbonyl group, methylnaphthyloxycarbonylgroup and methoxynaphthyloxycarbonyl group.

Examples of the aralkyloxycarbonyl group of the aralkyloxycarbonyl groupwhich may be substituted include aralkyloxycarbonyl groups having 8 to16 carbon atoms. Specific examples of the aralkyloxycarbonyl group whichmay be substituted include a benzyloxycarbonyl group,phenethyloxycarbonyl group, naphthylmethyloxycarbonyl group,α-methylbenzyloxycarbonyl group, 4-methylbenzyloxycarbonyl group and4-methoxybenzyloxycarbonyl group.

Examples of the ring formed by a combination of R⁴ and R⁵ or R⁵ and R⁶together with a carbon atom having a double bond include a cyclopentenering, cyclohexene ring, cyclooctene ring, 2-bornene ring, 2-norbornenering, 1-menthene ring and indene ring.

As for the alkenyl esters or alkenyl ethers used as raw materials, whichare represented by the formula (I), a commercially available product maybe used either as it is or after purified appropriately accordingly, ora compound produced by a known general production method may be used.

Further, the optically active ligand used in the present invention isexplained.

One of the optically active ligands to be used in the present inventionis an optically active phosphine compound represented by the aboveformula (II).

Examples of the phenyl group that may be substituted which isrepresented by Ar¹ or Ar² in the formula (II), include a phenyl groupand phenyl groups which may be substituted with an alkyl group having 1to 4 carbon atoms or alkoxy group having 1 to 4 carbon atoms at one orplural positions.

Examples of the ring where R⁷ and R⁸ and/or R⁹ and R¹⁰ are combined witheach other to form a ring in the formula (II) include a benzene ring, inwhich a trimethylene group, tetramethylene group, methylenedioxy groupor the like may be formed.

Examples of one of the optically active ligands used in the presentinvention is an optically active salene compound represented by theabove formula (III).

Examples of the alkyl group represented by R¹³, R¹⁴, R¹⁵ and R¹⁶ in theformula (III) include lower alkyl groups having 1 to 4 carbon atoms.Specific examples of these lower alkyl groups include a methyl group,ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutylgroup, sec-butyl group and tert-butyl group.

A further one of the optically active ligands used in the presentinvention is an optically active bisoxazoline compound represented bythe above formula (IV).

Examples of the alkyl group represented by R¹⁷ or R¹⁸ in the formula(IV) include lower alkyl groups having 1 to 4 carbon atoms. Specificexamples of these alkyl groups include a methyl group, ethyl group,n-propyl group, isopropyl group, n-butyl group, isobutyl group,sec-butyl group and tert-butyl group.

The remaining one of the optically active ligands used in the presentinvention is an optically active oxazoline compound represented by theformula (V).

Examples of the phenyl group that may be substituted, which isrepresented by Ar³ in the formula (V), include a phenyl group and phenylgroups which may be substituted with an alkyl group having 1 to 4 carbonatoms, alkoxy group having 1 to 4 carbon atoms or the like at one orplural positions.

Further, the alkyl group represented by R¹⁹ include lower alkyl groupshaving 1 to 4 carbon atoms. Specific examples of these alkyl groupsinclude a methyl group, ethyl group, n-propyl group, isopropyl group,n-butyl group, isobutyl group, sec-butyl group and tert-butyl group.

The transition metal complex used in the production process of thepresent invention can be easily obtained by mixing and stirring theoptically active compound represented by any one of the above formulae(II) to (V) with a transition metal compound in an appropriate solventwhich does not react with the compounds in the system under an inert gasatmosphere such as argon or nitrogen, under heating if required, and bytreatment according to the conventional method such as concentration,recrystallization and crystallization after the reaction is completed.

Also, the transition metal complex thus obtained according to thepresent invention may be further reacted with other ligands to makeother desired transition metal complexes. The reaction in this case isusually conducted in a solvent at room temperature under the atmosphere.The after treatments and the like after the reaction is the same asabove.

The transition metal compounds used in the present invention arepreferably compounds of a transition metal of IX group to XII group,more preferably compounds of a transition metal of IX group, X group orXII group. The compounds such as cobalt, palladium, platinum or mercuryor the like are particularly preferable.

Preferable examples of the transition metal compound used in the presentinvention include cobalt compounds, palladium compounds, platinumcompounds and mercury compounds as mentioned above. Specific examples ofthe cobalt compounds include hydrates or non-hydrates of divalent ortrivalent cobalt compounds such as cobalt acetate, cobaltacetylacetonate, cobalt chloride, cobalt bromide, cobalt carbonate,cobalt nitrate and cobalt sulfate.

Specific examples of the palladium compound include zero-valent ordivalent palladium compounds such as palladium chloride, palladiumacetate, dichlorobis(acetonitrile)palladium,dichlorobis(benzonitrile)palladium,dichlorobis(triphenylphosphine)palladium,tris(dibenzylideneacetone)palladium,dichloro(1,5-cyclooctadiene)palladium, palladiumbishexafluoropentanedionate and palladium bispentanedionate.

Specific examples of the platinum compound includedichlorobis(acetonitrile)platinum, dichloro(1,5-cyclooctadiene)platinum,chlorotetramine platinum hydrate and potassium tetrachloroplatinate.

Specific examples of the mercury compounds include mercuric acetate,mercuric sulfate and mercuric trifluoroacetate.

The transition metal complex according to the present invention caneffect sufficiently when it is used in a catalytic amount based on thealkenyl ester or alkenyl ether which is used as starting material in theproduction process of the present invention. Further, an opticallyactive compound having higher optical purity may be obtained by usingtwo or more transition metal complexes each consisting of a differentmetal in combination. Such use is also one of preferable embodiments.

The amount of the transition metal complex according to the presentinvention is usually 10 mol % enough to satisfy the requirements.

The amount of water used in the production process of the presentinvention is usually 1 to 10 equivalents, preferably 1 to 5 equivalentsbased on the alkenyl ester or alkenyl ether.

The reaction according to the present invention usually proceeds in anorganic solvent though it proceeds in no solvent insofar as the rawmaterial alkenyl ester or alkenyl ether is not a solid.

Any solvent may be used, and a solvent miscible with water ispreferable. However, when the substrate is present in a highconcentration, water is made into a separated state and the reactionproceeds even in this state.

Specific examples of the solvent used according to the present inventioninclude, but are not limited to, alcohols such as methanol, ethanol,n-propanol, isopropanol, n-butanol, t-butanol and methoxyethanol, cyclicor non-cyclic ethers such as dioxane, tetrahydrofuran anddimethoxyethane, acetonitrile and N,N-dimethylformamide.

The reaction may not proceed at an advantageous rate at extremely lowtemperature, and the transition metal complex may be decomposed atextremely high temperature. Therefore, the reaction is usually conductedat 0 to 100° C., preferably at 20 to 90° C.

The reaction time is usually dozens of minutes to dozens of hours,though it differs depending on the type and amount of the alkenyl esteror alkenyl ether used as a raw material, the type and amount of thetransition metal complex, the reaction temperature, other conditions andthe like.

The reaction according to the present invention proceeds in the presenceof oxygen, for example, in the air. However, as for some kinds of rawmaterials and products which are sensitive to oxygen, it is desirable toinduce a reaction under an inert gas atmosphere such as an argon ornitrogen atmosphere, excluding air and oxygen.

The treatment after the reaction can be easily completed in a propercombination of known after treating methods such as filtration, solventrecovery, various chromatographies, distillation and recrystallization,and isolation and purification of products and the like.

According to the present invention, the part unconverted into opticallyactive carboxylic acids or optically active alcohols among the compoundsrepresented by the formula (I) is obtained as optically activator of thecompounds represented by the formula (I).

Thus, the production process of the present invention is a process ofproducing an optically activator of alkenyl esters or alkenyl ethersrepresented by the formula (I) as well as process of producing anoptically active compound represented by the formula (VI).

It is therefore possible to obtain richer optically activator of alkenylesters or alkenyl ethers represented by the formula (I) by conducting areaction changing various reaction conditions, the type and molar ratioof the complex, the amount of water and the type of solventappropriately.

All the content described in the specification of Japanese PatentApplication No. 2003-52187 is incorporated in this specification.

EXAMPLES

The present invention is described more specifically by the followingexamples and reference examples, but not limited by these examples andreference examples.

In the following examples, the conversion rate and optical purity weremeasured by gaschromatography (GC). Gas chromatograph: Ajirent GC-6850mounted with Capillarycolumn: CYCLODEX-B (0.25 mmφ×30 m) was used. Theproduct was identified by using a NMR spectrum(Bruker ARX400.Incidentally, the Ph group represents a phenyl group.

Reference Example 1

[(R,R)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine](hereinafter, referred to as L³ when it is a ligand of a complex) (10.9g, 20.0 mmol) was dissolved in dichloromethane (80mL), the solution wasadded to a methanol solution (80 mL) of cobalt acetate tetrahydrate(5.98 g, 24.0 mmol), the mixture was stirred at room temperature for 15minutes, and as a result, a red solid was precipitated. After stirred at0° C. for 30 minutes, the red solid was collected and dried to obtainCo(L³) (11.6 g, red solid) (yield: 96%).

Reference Example 2

Two equivalents of acetic acid was added to a Co(L³) toluene solution(about 1 M) and the mixture was stirred under the atmosphere.Thereafter, toluene was distilled under reduced pressure to obtainCo(OAc) (L³) in a quantitative yield.

Example 1

A mixture of 360 mg (2 mmol) of 2-bornyl vinyl ether and 16 mg (0.02mmol) of Hg(L¹) (OCOCF₃)₂ was dissolved in 0.5 ml of 2-propanol underthe atmosphere, 0.09 mL (5 mmol) of water was added to the mixture, andthe mixture was then stirred at room temperature for 45 minutes. Thereaction mixture was analyzed By GC, to find that 2-bornyl vinyl etherwas converted into an optically active borneol at a conversion rate of99.8% and with an optical purity of 23% ee.

Example 2

A mixture of 336 mg (2 mmol) of vinyl α-methoxyphenylacetate and 14.8 mg(0.04 mmol) of PdCl²(L²) was dissolved in 2-propanol under theatmosphere, 0.09 mL (5 mmol) of water was added to the mixture, and themixture was then stirred at 80° C. for 6 hours. The reaction mixture wasanalyzed By GC, to find that vinyl α-methoxyphenylacetate was convertedinto an optically active α-methoxyphenylacetic acid at a conversion rateof 90% and with an optical purity of 12% ee.

Example 3

168 mg (0.92 mmol) of 2-tert-butylcyclohexyl vinyl ether and 30 mg(0.046 mmol) of Co(OAc) (L³) were dissolved in 0.5 ml of 2-propanolunder the atmosphere, 10.7 mg (0.00.92 mmol) of [Pt(L⁴) (H₂O)₂](BF₄)₂was added to the mixture. After the mixture was stirred, 45 μL (2.5mmol) of water was added to the resulting mixture, and the mixture wasthen heated to 60° C. After 6 hours, the reaction solution was analyzedby GC, to find that 20% of the 2-tert-butylcyclohexyl vinyl ether wasleft with an optical purity of 80.8% ee and comprised (1R, 2S) isomers.At the same time, 80% of 2-tert-butyrocyclohexanol was produced whichhad an optical purity of 8.2% ee and comprised (1R, 2S) isomers.

Bound and conjugated with a cobalt atom through oxygen and nitrogen

Example 4

91 mg (0.5 mmol) of 2-tert-butylcyclohexyl vinyl ether, 6.6 mg (0.01mmol) of Co(OAc) (L⁵) and 1.8 mg (0.01 mmol) of potassiumtrifluoromethanesulfonate were dissolved in 0.5 ml of 2-propanol underthe atmosphere. After the mixture was stirred, 45 μL (2.5 mmol) of waterwas added to the mixture and the mixture was then heated to 60° C. After45 hours, the reaction solution was analyzed by GC, to find that 12% ofthe 2-tert-butylcyclohexyl vinyl ether was left with an optical purityof 91.5%ee and comprised (1S, 2R) isomers. At the same time, 83% of2-tert-butyrocyclohexanol was produced which had an optical purity of20% ee and comprised (1R, 2S) isomers.

Bound and conjugated with a cobalt atom through oxygen and nitrogen

Example 5

1.09 g (6.00 mmol) of cis-2-tert-butylcyclohexyl vinyl ether and 199 mg(0.30 mmol) of Co(OAc) (L³) were dissolved in 6.0 ml of methanol underthe atmosphere and 540 μL (30 mmol) of water was added to the mixtureand the mixture was then stirred at 20° C. After 11 hours, the reactionsolution was analyzed by GC, to find that 23% of thecis-2-tert-butylcyclohexyl vinyl ether was left with an optical purityof 92%ee and comprised (1R, 2R) isomers. Further, the reaction solutionwas purified by silica gel column chromatography to isolate the reactionsubstrate 2-tert-butylcyclohexyl vinyl ether and the reaction product2-tert-butylcyclohexanol in a ratio of 22% and 77% respectively. Also,the k_(re1) value showing the selectivity of reactions at this time was4.9.

The reaction speed ratio k_(re1) of both mirror isomers showing theselectivity was calculated according to the following equation (the sameto all the following examples)k _(re1)=1n[(1−conv) (1−ee)]/1n[(1−conv) (1+ee)]

(where ee is the excess rate of the unreacted substrate and convrepresents a conversion rate of the reaction)

Example 6

The reaction was conducted in the same manner as in Example 5 exceptthat the reaction temperature was altered to −10° C. and the reactiontime was altered to 103 hours. The obtained reaction solution wasanalyzed by GC, to find that 32% of the cis-2-tert-butylcyclohexyl vinylether was left with an optical purity of 91% ee. Further, the reactionsolution was purified by silica gel column chromatography to obtain thereaction product 2-tert-butylcyclohexanol in a yield of 68%. Also, thek_(re1) value showing the selectivity of reactions at this time was 7.4.

Example 7

The reaction was conducted in the same manner as in Example 5 exceptthat the Co complex was altered to Co(L³) and the reaction time wasaltered to 140 hours. The obtained reaction solution was analyzed by GC,to find that 25% of the cis-2-tert-butylcyclohexyl vinyl ether was leftwith an optical purity of 94% ee. Further, the reaction solution waspurified by silica gel column chromatography to obtain the reactionproduct 2-tert-butylcyclohexanol in a yield of 75%. Also, the k_(re1)value showing the selectivity of reactions at this time was 5.8.

Reference Example 3

5.8 mg (0.025 mmol) of 2,4-dinitrophenol (containing 20% water) and 15.1mg (0.025 mmol) of Co(L³) were dissolved in 50 μl of toluene and themixture was stirred at room temperature (20° C.) for 1 hour under theatmosphere. Thereafter, toluene was distilled under reduced pressure toobtain a Co[OC₆H₃(2,4-(NO₂)₂)](L³) complex. The obtained complex wasused in the following reaction as it was without purified.

Example 8

The Co complex obtained in Reference Example 3 and 91.5 mg (0.50 mmol)of cis-2-tert-butylcyclohexyl vinyl ether were dissolved in 0.5 ml ofmethanol and 45 μL (2.5 mmol) of water was added to the mixture, and themixture was then stirred at −10° C. After 77 hours, the reactionsolution was analyzed by GC, to find that 38% of thecis-2-tert-butylcyclohexyl vinyl ether (1a) was left with an opticalpurity of 90% ee and comprised (1R, 2R) isomers. Further, the reactionsolution was purified by silica gel column chromatography to obtain thereaction product 2-tert-butyrocyclohexanol in a yield of 62%. Also, thek_(re1) value showing the selectivity of reactions at this time was10.0.

Example 9

The reaction was conducted in the same manner as in Example 8 exceptthat the cleavage reaction temperature of the vinyl ether was altered to20° C. and the reaction time was altered to 10 hours. The obtainedreaction solution was analyzed by GC, to find that 27% of thecis-2-tert-butylcyclohexyl vinyl ether was left with an optical purityof 90% ee. Further, the reaction solution was purified by silica gelcolumn chromatography to obtain the reaction product2-tert-butyrocyclohexanol in a yield of 73%. Also, the k_(re1) valueshowing the selectivity of reactions at this time was 5.4.

Example 10

183 mg (1.00 mmol) of DL-menthyl vinyl ether and 19.9 mg (0.030 mmol) ofCo(OAc) (L³) were dissolved in 1.0 ml of 2-propanol under the atmosphereand 90 μL (5.0 mmol) of water was added to the mixture, and the mixturewas then stirred at −10° C. After 10 hours, the reaction solution wasanalyzed by GC, to find that 32% of the menthyl vinyl ether was leftwith an optical purity of 92%ee and comprised (1R, 2S, 5R) isomers.Further, the reaction solution was purified by silica gel columnchromatography to isolate the reaction substrate menthyl vinyl ether andthe reaction product menthol in a ratio of 28% and 68% respectively.Also, the krel value showing the selectivity of reactions at this timewas 7.8.

Example 11

The reaction was conducted in the same manner as in Example 10 exceptthat the reaction temperature was altered to 20° C. and the reactiontime was altered to 3 hours. The obtained reaction solution was analyzedby GC, to find that 32% of the menthyl vinyl ether was left with anoptical purity of 79% ee. Further, the reaction solution was purified bysilica gel column chromatography to obtain the reaction product mentholin a yield of 68%. Also, the k_(re1) value showing the selectivity ofreactions at this time was 4.9.

Example 12

The reaction was conducted in the same manner as in Example 10 exceptthat methanol was used in stead of the solvent 2-propanol, the reactiontemperature was altered to 20° C. and the reaction time was altered to 1hour. The obtained reaction solution was analyzed by GC, to find that27% of the menthyl vinyl ether was left with an optical purity of 58%ee. Further, the reaction solution was purified by silica gel columnchromatography to obtain the reaction product menthol in a yield of 73%.Also, the k_(re1) value showing the selectivity of reactions at thistime was 2.5.

Example 13

The reaction was conducted in the same manner as in Example 10 exceptthat methanol was used instead of the solvent and the reaction time wasaltered to 2 hours. The obtained reaction solution was analyzed by GC,to find that 12% of the menthyl vinyl ether was left with an opticalpurity of 76% ee. Further, the reaction solution was purified by silicagel column chromatography to obtain the reaction product menthol in ayield of 88%. Also, the k_(re1) value showing the selectivity ofreactions at this time was 2.3.

Example 14

62.4 mg (0.20 mmol) of O-vinylnaphthol and 1.3 mg (0.002 mmol) of Co(OAc) (L³) were dissolved in 50 μl of methanol under the atmosphere, 18μl (1.0 mmol) of water was added to the mixture, and the mixture wasthen stirred at −10° C. After 5 hours, the reaction solution wasanalyzed by HPLC, to find that 89% of the O-vinylnaphthol was left withan optical purity of 10% ee. Further, the reaction solution was purifiedby silica gel column chromatography to obtain the reaction productbinaphthol in a yield of 11%. Also, the k_(re1) value showing theselectivity of reactions at this time was 11.0.

Example 15

30.4 mg (0.086 mmol) of 2-acetyloxy-2′-vinyloxy1,1′-binaphthyl and 2.8mg (0.004 mmol) of Co (OAc) (L³) were dissolved in 90 μl of a mixedsolvent (2:1) of methanol and THF under the atmosphere and 8 μl (0.44mmol) of water was added to the mixture, and the mixture was thenstirred at 0° C. After 10 hours, the reaction solution was analyzed byHPLC, to find that 66% of the 2-acetyloxy-2′-vinyloxy1,1′-binaphthyl wasleft with an optical purity of 44% ee. Further, the reaction solutionwas purified by silica gel column chromatography to obtain the reactionproduct O-acetylbinaphthol in a yield of 34%. Also, the k_(re1) valueshowing the selectivity of reactions at this time was 20.7.

Example 16

95.8 mg (0.27 mmol) of 2-acetyloxy-2′-vinyloxy1,1′-binaphthyl and 9.0 mg(0.014 mmol) of Co(OAc) (L³) were dissolved in 0.27 ml of a mixedsolvent (2:1) of methanol and THF under the atmosphere, 25 μl (1.44mmol) of water was added to the mixture, and the mixture was thenstirred at 0° C. After 21 hours, the reaction solution was purified bysilica gel column chromatography and as a result, 34% of2-acetyloxy-2′-vinyloxy-1,1′-binaphthyl was left with an optical purityof 86%ee measured by HPLC. The reaction product O-acetylbinaphthol wasobtained in a yield of 66%. Also, the k_(re1) value showing theselectivity of reactions at this time was 6.6.

Example 17

The reaction was conducted in the same manner as in Example 16 exceptthat 2-tert-butyldiphenylsilyloxy-2′-vinyloxy-1,1′-binaphthyl was usedinstead of 2-acetyloxy-2′-vinyloxy-1,1′-binaphthyl, the reactiontemperature was altered to 20° C. and the reaction time was altered to22 hours. The reaction solution was purified by silica gel columnchromatography and as a result, 67% of the2-tert-butyldiphenylsilyloxy-2′-vinyloxy-1,1′-binaphthyl was left withan optical purity of 38% ee. Also, the reaction productO-acetylbinaphthol was obtained in a yield of 33%. Also, the k_(re1)value showing the selectivity of reactions at this time was 12.7.

INDUSTRIAL APPLICABILITY

The present invention provides a process of producing an opticallyactive compound by utilizing a hydrolysis of alkenyl esters or acleavage of alkenyl ethers. The reaction can be conducted in a highconcentration, unnecessary to use an acidic compound or a basiccompound, also unnecessary to use a buffer solution or nutrient sourcesunlike an enzymatic reaction and a reaction using microorganisms and anoptically active carboxylic acid or alcohol can be easily obtained froma raw material of racemic isomer.

Further, according to the production process of the present invention,optically activator of alkenyl esters or alkenyl ethers can be produced,and it is also possible to obtain the optical activator of alkenylesters or alkenyl ethers richer by conducting a reaction changingvarious reaction conditions, the type and molar ratio of the complex,the amount of water and the type of solvent appropriately.

1. A process for producing an optically active compound represented bythe following formula (VI), the process comprising reacting water with acompound represented by the following formula (I) in the presence of oneor more transition metal complexes having, as a ligand, an opticallyactive compound represented by the following formula (II), (III), (IV)or (V):

(wherein R¹, R² and R³, which are different from each other, represent ahydrogen atom, a straight-chain, branched-chain or cyclic alkyl groupwhich may be substituted, a straight-chain, branched-chain or cyclicalkenyl group which may be substituted, a straight-chain orbranched-chain alkoxy group which may be substituted, an aralkyl groupwhich may be substituted, an aryl group which may be substituted, aheterocyclic group which may be substituted, a straight-chain orbranched-chain alkoxycarbonyl group which may be substituted, anaralkyloxy group which may be substituted, an alkanoyloxy group whichmay be substituted, an alkylthio group which may be substituted, anaralkylthio group which may be substituted, a benzoyloxy group which maybe substituted, a tri-substituted silyloxy group, an amino group whichmay be substituted, a hydroxyl group, a tetrahydropyran-2-yloxy group ora mercapto group: any two of R¹, R² and R³ may form a ring which maycontain a heteroatom therein; and R⁴, R⁵ and R⁶ each independentlyrepresent a hydrogen atom, a straight-chain, branched-chain or cyclicalkyl group which may be substituted, a straight-chain, branched-chainor cyclic alkenyl group which may be substituted, an aralkyl group whichmay be substituted, an aryl group which may be substituted, aheterocyclic group which may be substituted, a straight-chain orbranched-chain alkoxycarbonyl group which may be substituted, anaryloxycarbonyl group which may be substituted or an aralkyloxycarbonylgroup which may be substituted; R⁴ and R⁵ or R⁵ and R⁶ may be combinedwith each other together with an adjacent carbon atom having a doublebond to form a ring; and A represents a methylene group, a carbonylgroup or a single bond);

(wherein Ar¹ and Ar² each independently represent a phenyl group whichmay be substituted, R⁸ and R⁹ each independently represent a methylgroup or a methoxy group, and R⁷ and R¹⁰ represent a hydrogen atom; R⁷and R⁸ and/or R⁹ and R¹⁰ may be combined with each other to form a ringwhich may contain a heteroatom therein);

(wherein R¹¹ and R¹² each independently represent a hydrogen atom or amethyl group, R¹³ R¹⁴ R¹⁵ and R¹⁶ each independently represent ahydrogen atom or an alkyl group and, * represents an asymmetric carbonatom);

(wherein R¹⁷ and R¹⁸ each independently represent an alkyl group or aphenyl group and, * represents an asymmetric carbon atom);

(wherein R¹⁹ represents an alkyl group or a phenyl group, Ar³ representsa phenyl group which may be substituted, and * represents an asymmetriccarbon atom), and

(wherein R¹, R² and A have the same meanings as above, and * representsan asymmetric carbon atom.)
 2. A production process according to claim1, wherein A is a carbonyl group in the formulae (I) and (VI).
 3. Aproduction process according to claim 1, wherein A is a methylene groupor a single bond in the formulae (I) and (VI).
 4. A production processaccording to claim 1, wherein the transition metal complex is a complexof a transition metal of IX to XII groups in the periodic table.
 5. Aproduction process according to claim 4, wherein the complex of thetransition metal of IX to XII groups in the periodic table is a complexof a transition metal of IX, X or XII group.
 6. A production processaccording to claim 5, wherein the transition metal of IX group in theperiodic table is cobalt.
 7. A production process according to claim 5,wherein the transition metal of X group in the periodic table ispalladium or platinum.
 8. A production process according to claim 5,wherein the transition metal of XII group in the periodic table ismercury.
 9. A production process according to claim 1, wherein thereaction is conducted in an organic solvent.
 10. A production processaccording to claim 1, the process comprising producing an opticallyactivator of a compound represented by the formula (I) at the same time.